Ramelteon - CAS 196597-26-9

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CAS 196597-26-9 Ramelteon
White or off-white powder
Reference Reading
1. Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist, agomelatine,on the rat sleep–wake cycle architecture
Amandine Descamps & Colette Rousset & Mark Millan & Michael Spedding & Philippe Delagrange & Raymond Cespuglio. Psychopharmacology (2009) 205:93–106
One major structure expressing both MT1 and MT2 receptors is the suprachiasmatic nucleus that participates in the regulation of sleep–wake-function, at least partially via an indirect projection from to the noradrenergic locus coeruleus that controls arousal (Aston-Jones et al. 2001). However, the neuronal substrates underlying the influence of melatoninergic mechanisms upon REM sleep require direct evaluation. Mimicking the modest influence of melatonin upon REM sleep, a mild influence upon REM sleep (albeit limited in magnitude and duration as compared with agomelatine) was also seen with ramelteon, a synthetic and selective MT1 and MT2 receptor agonist used to treat insomnia. This effect, and its modest increase in SWS, corresponds to published data, though it is unclear why the influence of ramelteon and melatonin on SWS sleep and waking differ (Miyamoto et al. 2004; Erman et al. 2006; Borja and Daniel 2006).
2. The effects of acute treatment with ramelteon, triazolam, and placebo on driving performance, cognitive function, and equilibrium function in healthy volunteers
Akemi Miyata & Kunihiro Iwamoto & Naoko Kawano & Kunihiro Kohmura. Psychopharmacology (2015) 232:2127–2137
Unlike the benzodiazepine receptor agonists, ramelteon is one of the novel classes approved by FDA for the treatment of insomnia. Ramelteon, a MT1/MT2 melatonin receptor agonist, shows higher affinities for these receptors than does the natural ligand (Pandi-Perumal et al. 2007). Because ramelteon helps to promote sleep and circadian rhythm entrainment without significant interaction with GABA-benzodiazepine and muscarinic receptors, ramelteon is expected to have minimal effect on sedation and cognitive function. Several lines of evidences showed that ramelteon has no detrimental effects on psychomotor and cognitive performance (Erman et al. 2006; Johnson et al. 2006; Karim et al. 2006; Mayer et al. 2009;Rothetal. 2005; Zammit et al. 2007, 2009a, 2009b), but more recent studies demonstrated that ramelteon significantly impaired psychomotor performance and cognitive function including driving performance (Cohen et al. 2010;Metsetal. 2011). Therefore, the effects of ramelteon on these activities are controversial. The subjects of the studies that showed that ramelteon did not impair performances are substance abusers or insomnia patients, while the subjects of the studies that showed that ramelteon impaired performances are healthy subjects. The difference of the subjects’ characteristics may contribute to these results. Additional investigations are urgently needed to elucidate the effect of ramelteon on functional ability; however, there is little research concerning the effect of ramelteon on daily living including automobile driving. According to the results of the recent studies, we hypothesized that ramelteon would influence cognitive function including driving performance in the healthy subjects.
3. Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea
Meir Kryger & Sherry Wang-Weigand & Thomas Roth. Sleep Breath (2007) 11:159–164
Ramelteon is a nonsedating chronohypnotic indicated for the treatment of insomnia. Unlike benzodiazepine receptor agonists, which act as broad CNS depressants and are sedative, ramelteon is highly selective for MT1 and MT2 receptors, which are located primarily in the suprachiasmatic nucleus of the hypothalamus, and does not produce general sedative effects. In the present study, the safety of ramelteon was evaluated in subjects with mild to moderate obstructive sleep apnea.
4. Effect of Ramelteon, a selective MT1/MT2-receptor agonist, on respiration during sleep inmild tomoderate COPD
Meir Kryger & Sherry Wang-Weigand & Jeffrey Zhang & Thomas Roth. Sleep Breath (2008) 12:243–250
Ramelteon is a novel chronohypnotic used for the treatment of insomnia. The recommended therapeutic dose is 8 mg for adults and older adults. Unlike the hypnotics that act at gamma-aminobutyric acid (GABA)A–benzodiaz-epine receptor complexes located throughout the central nervous system (CNS), ramelteon has a unique mechanism based on a high selectivity for the melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus (SCN). The SCN is located within the hypothalamus and is known to regulate the body’s circadian rhythms, including the sleep–wake cycle. Studies indicate that the MT1 receptor mediates the acute inhibition of SCN firing by melatonin, and activity at the MT2 receptor has been associated with the phase-shifting effects of melatonin on circadian rhythms. Ramelteon has minimal affinity for the following CNS binding sites: GABA, benzodiazepine, opioid, acetylcholine, histamine, dopamine receptors, and ion channels and transporters. Ramelteon is rapidly absorbed after oral administration, with peak serum concentrations at less than 1 h.
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